Masahiro Hoso

Microstructure and development of the normal and pathologic biliary tract in humans, including blood supply.

Microstructure and development of the normal biliary tract and the pathologies of several biliary tract diseases in humans are reviewed. The biliary tract, comprising the bile duct and peribiliary glands, is anatomically divided into the extrahepatic and intrahepatic biliary tree. The intrahepatic biliary tree is further divided into large bile ducts, corresponding to the right and left hepatic ducts and their first to third order branches, and into septal and interlobular bile ducts and bile ductules according to their size and location relative to the hepatic lobules and surrounding structures. The right and left hepatic ducts and the extrahepatic bile ducts are composed of dense fibrous duct walls lined by a layer of columnar biliary epithelium. The peribiliary glands, which may secrete mucinous and serous substances into the bile, are found along the extrahepatic and large intrahepatic bile ducts. They are divided in glands within and outside the duct wall. The former (intramural glands) drain directly into the lumen of the bile duct, while the latter (extramural glands) are composed of several lobules and drain into the ductal lumen via their own conduits. The biliary tract is supplied by a complex vasculature called the peribiliary vascular plexus. Afferent vessels of this plexus derive from hepatic arterial branches, and this plexus drains into the portal venous system or directly hepatic sinusoids. The development of the intrahepatic biliary tract is divided into three stages: the stage of the ductal plate, the stage of biliary cell migration into the mesenchyme, and the stage of bile duct formation in the portal tract. It remains unclear how the extrahepatic and intrahepatic biliary tract integrate. Along with these developmental changes in the biliary tract, the peribiliary glands and the vascular plexus also develop in a step‐wise manner and their maturation is completed after birth. Pathologies of various biliary diseases are briefly reviewed noting their relevance to several histologic elements and the microenvironment of the biliary tract and the developmental anomalies of the biliary tract including ductal plate malformation. Microsc. Res. Tech., 38:552–570, 1997.

Histopathology of the liver in non-cirrhotic portal hypertension of unknown aetiology.

Non‐cirrhotic, long‐standing portal hypertension of unknown aetiology is being re‐evaluated histopathologically and clinically. In this study, we examined 107 livers with this condition (92 wedge biopsy and 15 autopsy specimens) from five institutions in Japan. These cases were histologically categorized into four groups: idiopathic portal hypertension (66 cases), nodular regenerative hyperplasia (14 cases), partial nodular transformation (two cases), and incomplete septal cirrhosis (25 cases). These four groups shared several histological features: dense portal fibrosis with portal venous obliteration and intralobular slender fibrosis. In addition, the histopathological features characteristic of one group were also found to a mild degree in other groups. The histopathological lesions preceding portal venous obliteration remain speculative. However, the portal venous obliteration may be responsible for the occurrence of sustained portal hypertension and several of the pathological changes in these livers. It seems likely that idiopathic portal hypertension, nodular regenerative hyperplasia, partial nodular transformation and incomplete septal cirrhosis comprise a family of non‐cirrhotic, long‐standing portal hypertension in Japan, and the histological differences between them may reflect chronological progression of a single disease.

Intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis : report of an autopsy case

We report an autopsy case of a 60-year-old woman who had congenital hepatic fibrosis with intrahepatic cholangiocarcinoma. A white nodular lesion with a surrounding vague gray area was detected in the right lobe of the liver. Microscopically, most of the nodular lesion was a poorly-differentiated adenocarcinoma. In the surrounding gray area, small bile ducts and bile ductules showed prominent epithelial overgrowth, some of which was composed of dysplasia and well-differentiated adenocarcinoma. The background liver showed the characteristic features of congenital hepatic fibrosis. Immunohistochemically, biliary oncofetal markers (mucin core protein 1 and carcinoembryonic antigen) were more frequently and extensively expressed in poorly-differentiated than well-differentiated adenocarcinoma. This is the 4th reported case of intrahepatic cholangiocarcinoma arising in congenital hepatic fibrosis and suggests that malignant transformation via dysplasia occurs in the abnormal intrahepatic biliary tree of older congenital hepatic fibrosis patients.

Fatty macroregenerative nodule in non-steatotic liver cirrhosis. A morphologic study.

We here describe the morphologies of 9 macroregenerative nodules (MRNs) showing moderate to marked fatty change (fatty MRN) from 6 cases of non- or minimally-steatotic cirrhotic livers. In most of these cases, no obvious steatogenic factors of the liver were obtainable. These fatty MRNs showed more or less a sharp border. Seven of these fatty MRNs showed a variable degree of unusual morphological alterations suggestive of neoplasia: atypical and hyperchromatic nuclei, abnormal blood vessels, foci of clustering Mallory bodies, numerous hyaline globules, α-fetoprotein-positive hepatocytes, resistance to iron accumulation, infiltration into the portal tracts within MRN, and occurrence of hepatocellular carcinoma without fatty change. These observations suggest that at least some of the fatty MRNs are neoplastic or belong to a borderline lesion, and that the fatty change in the MRNs may be one of hepatocellular expressions related to human hepatocarcinogenesis.

Mallory body clustering in adenomatous hyperplasia in human cirrhotic livers: Report of four cases

We report four cases of liver cirrhosis in which seven nodules of adenomatous hyperplasia (AH) were present. Each nodule contained one to several foci of hepatocytes with Mallory bodies (MBs). All of these foci were well-circumscribed lesions located within the nodules of AH. The cells containing MBs showed variable degrees of atypia. At least two of the foci were considered to represent a recent proliferation of the cells containing MBs, possibly premalignant foci, because they showed resistance to the accumulation of stainable iron in siderotic background. From these observations, it was suggested that the MB-containing hepatocellular clusters in AH might have occurred as the result of proliferation in small foci and that at least some of them may be related to hepatocarcinogenesis in humans.

Poorly differentiated (‘insular’) carcinoma of the thyroid

Three cases of unusual poorly differentiated (‘insular’) carcinoma of the thyroid gland are presented. These three thyroid carcinomas were large; the tumors from patients 1 and 3 were encapsulated, and that from patient 2 showed invasive growth. Microscopically the tumors were characterized by welldefined solid nests (insulae), which were composed of rather small and uniform tumor cells with round to oval nuclei. Formation of small and colloid‐containing follicles was associated with these nests to varying degrees. The tumors of patients 1 and 3 were composed entirely of insular components, but that of patient 2 was associated with small areas of welldifferentiated follicular carcinoma. The metastatic tumors of patients 1 and 2 were essentially similar to the primary with small foci of follicular carcinoma.

Microvasculature in the small portal tracts in idiopathic portal hypertension. A morphological comparison with other hepatic diseases.

The morphology of the microvasculature in the small portal tracts was examined in normal livers, idiopathic portal hypertension (IPH) and other hepatic diseases. The microvasculature examined was arbitrary divided into two groups: that near the limiting plate and that within portal tracts, particularly around bile ducts. Based on comparisons of histology, immunohistochemistry and vascular casts, it is suggested that the former corresponded to inlet venules and the latter to distributing portal veins and peribiliary capillary plexus. Both of these microvasculatures were positive forUlex europaeus lectin I, and (infrequently and weakly) for factor VIII-related antigen. Morphometry disclosed that inlet venules were reduced in number in IPH compared with normal livers and that distributing portal veins, peribiliary capillary plexus and inlet venules were increased in extrahepatic portal obstruction, chronic active hepatitis and extrahepatic obstructive cholestasis. We believe that the change in the microvasculature reflects abnormal microcirculation in the small portal tracts, and that the reduction of inlet venules plays an important role in the development of portal hypertension in IPH.

Cytophotometric DNA analysis of adenomatous hyperplasia in cirrhotic livers

The possibility of adenomatous hyperplasia (AH) being a precusor lesion of hepatocellular carcinoma (HCC) in human cirrhotic livers was investigated. Feulgen DNA cytophotometry was used to measure the DNA content of the hepatocytes in 13 AH nodules obtained from six cirrhotic livers. DNA distribution patterns were classified into types I (diploid pattern), II (hyperploid pattern) and III (aneuploid pattern). According to the cellular and structural atypia, AH nodules were divided into ordinary type (2 nodules) and atypical type (11 nodules), 6 of the latter possessing foci of apparent HCC within them. Two ordinary AH nodules showed a type I DNA distribution pattern, similar to the surrounding regenerative nodules. A major part of the atypical AH nodules also showed type I. However, small foci showing moderate and structural atypia within these atypical AH nodules presented a type I pattern with more hyperploid cells and some aneuploid cells and also a type II histogram pattern with some aneuploid cells. Neoplastic foci, found within 5 atypical AH nodules, displayed various patterns (type I, II, III) as seen in well-developed HCC nodules. These data may imply that atypical AH nodules are precursor lesions of HCC, or are actually undergoing malignant transformation. It is apparent that at least some HCCs occurring in liver cirrhosis evolve through AH.

Partial nodular transformation of the liver with portal vein thrombosis. A report of two autopsy cases.

Partial nodular transformation (PNT) of the liver is a rare condition in which nonfibrous nodules composed of hyperplastic hepatocytes replace the hepatic parenchyma around the hepatic hilus. We report two autopsy cases involving PNT of the liver with portal vein thrombosis. Case 1 was a 27-year-old man with malignant lymphoma. Ascites gradually increased, and he died 4 years after the onset of his illness. Case 2 was a 73-year-old woman treated for cirrhosis for 4 years who died of renal failure. Postmortem examination of these two cases revealed numerous coalescent nodules in the hilus of the liver as well as portal vein thrombus in the hilus. Microscopically, these nodules in the perihilar area were composed of hyperplastic hepatocytes without fibrous rim, and the peripheral parenchyma showed atrophy to some extent. The portal vein thrombi in the hilus and large portal tracts were mainly fresh and partially organized. Portal vein branches in the peripheral small portal tracts were devoid of significant pathologic changes. We suggest that PNT of the liver in our cases occurred as the result of uneven blood supply to the perihilar parenchyma due to portal vein thrombosis in the hepatic hilus.

Epithelioid Hemangioendothelioma of the Liver in Primary Biliary Cirrhosis

We report a case of primary epithelioid hemangioendothelioma of the liver occurring in a patient with primary biliary cirrhosis, stage III. The hepatic tumor was found incidentally by imaging techniques and was surgically resected under a tentative diagnosis of metastatic carcinoma. The resected tumor (1.8±1.6 cm) showed Wtcal histologic features of epithelioid hemangioendd jelioma. The tumor cells were positive for factor VIII related antigen and were stained with Ulex europaeus lectin I. Ultrastruc‐turally, the tumor cells showed cytoplasmic vacuoles, tight junctions, basal lamina, pinocytotic vesicles, bundles of thin filaments (approximately 10 nm in diameter) and Weibel Palade bodies. The non tumorous part of the liver showed features of primary biliary cirrhosis, stage III. This is the first reported case of epithelioid hemangioendothelioma occurring in a liver with primary biliary cirrhosis. Acta Pathol Jpn 39: 607 611, 1989.